Mitochondrial-targeted therapeutics in oral squamous cell carcinoma: molecular and therapeutic implications

Area of Science:

• Oncology
• Mitochondrial Biology
• Cancer Metabolism

Background:

• Oral squamous cell carcinoma (OSCC) frequently exhibits resistance to chemoradiation.
• Mitochondrial dysregulation, including mtDNA mutations and metabolic reprogramming, is implicated in OSCC resistance.
• Existing reviews often focus on downstream effects, lacking a mechanism-driven, organelle-specific approach.

Purpose of the Study:

• To provide a comprehensive review of mitochondria-directed therapeutic strategies for OSCC.
• To adopt a mechanism-driven framework focusing on mitochondrial vulnerabilities.
• To identify translational challenges and outline a roadmap for clinical development.

Main Methods:

• Systematic narrative review of existing literature.
• Focus on electron transport chain (ETC) function, mitochondrial apoptosis, and redox homeostasis.
• Distinguishing OSCC-specific findings from broader head and neck or solid tumor data.

Main Results:

• Candidate therapeutics targeting mitochondrial function and redox balance show promise.
• Significant barriers to clinical translation include intratumoral heterogeneity and poor tumor-selective delivery.
• Lack of validated predictive and pharmacodynamic biomarkers hinders clinical implementation.

Conclusions:

• Mitochondria-directed therapies offer a potential new avenue for treating resistant OSCC.
• Overcoming barriers in delivery and biomarker development is crucial for clinical success.
• A mechanism-informed, biomarker-enriched approach is essential for future clinical trials in OSCC.